title: Safety and efficacy of different lanreotide doses in the treatment of polycystic liver disease: pooled analysis of individual patient data.
abstract: BACKGROUND
  Long-acting lanreotide (LAN) 120 mg every 4 weeks reduces liver volume (LV) in patients with polycystic liver diseases (PCLD). Animal studies demonstrated that the inhibition of hepatic and renal cystogenesis is dose dependent.
  
  
  OBJECTIVE
  To investigate the safety and efficacy of two different LAN doses in PCLD patients.
  
  
  METHODS
  The 6-month results of the LOCKCYST I trial, its extension study and the LOCKCYST II trial were pooled. LV at baseline and month 6 was measured by CT-scan and blindly re-analysed by two independent radiologists.
  
  
  RESULTS
  The study population [132 treatment periods, age 49 years (IQR: 45-55), 114 women] consisted of three groups. Each received treatment every 4 weeks during 6 months: placebo (n = 26); LAN 90 mg (n = 55) or LAN 120 mg (n = 51). The inter-observer variability and agreement in the calculation of LV were excellent. Severe side effects occurred with placebo, LAN 90 mg and LAN 120 mg in respectively 0%, 7% and 16%. Change in LV's after 6 months in these three groups were respectively: increase of +36 mL [(-45)-(+138)]; decrease of -82 mL [(-285)-(+92)] and decrease of -123 mL [(-312)-(+4)] (Kruskal-Wallis One Way anova on Ranks; P = 0.002). Based on ROC analysis, a reduction of ≥120 mL in LV has a positive predictive value of 64% for improving symptoms (ROC analysis AUC: 0.729; sensitivity 73%, specificity 69%, P < 0.0001).
  
  
  CONCLUSIONS
  Both LAN 90 mg and LAN 120 mg reduce liver volume. LAN 90 mg has less side effects. This suggests that in case of intolerance to LAN 120 mg, a dose reduction to LAN 90 mg is meaningful.
authors.affiliation: Department and Laboratory of Hepatology, University Hospitals KULeuven, Leuven, Belgium. frederik.temmerman@uzleuven.be
authors.forename: F
authors.initials: F
authors.lastname: Temmerman
authors.forename: T
authors.initials: T
authors.lastname: Gevers
authors.forename: T A
authors.initials: TA
authors.lastname: Ho
authors.forename: R
authors.initials: R
authors.lastname: Vanslembrouck
authors.forename: W
authors.initials: W
authors.lastname: Coudyzer
authors.forename: J
authors.initials: J
authors.lastname: van Pelt
authors.forename: B
authors.initials: B
authors.lastname: Bammens
authors.forename: Y
authors.initials: Y
authors.lastname: Pirson
authors.forename: J P
authors.initials: JP
authors.lastname: Drenth
authors.forename: F
authors.initials: F
authors.lastname: Nevens
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003560:Cysts / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000009:adverse effects; D012372:ROC Curve; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin